tbuckley/cabot-search huggingface dataset:
Can collagen sheet work as a catalyst in the healing process of nonhealing ulcers with platelet-rich plasma membrane? – correspondence
Authors: Dev Desai
Journal: International Journal of Surgery (2023)

Final Year MBBS Student, NHL Municipal medical college, Ahmedabad, Gujarat Article type :- Letter to Editor Keywords: Non-healing ulcer, Platelet-rich plasma membrane, Platelet-derived growth factor Running title-PRP and collagen sheet in wound healing Submission type – Correspondence (Letter to editor) Disclosure - The authors declare no conflicts of interest." Being a letter to editor, the article has no patient data. All the research articles that have been cited by the authors has been already presented in the references list. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: 14, Jagannath Park, NR. Malav-talav, Jivaraj Park, Ahmedabad- 380051. Contact: +91-9173655551. E-mail address: [email protected] (D. H. Desai). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Preneoplastic stromal cells promote BRCA1-mediated breast tumorigenesis
Authors: Kevin Nee, Dennis Ma, Quy H. Nguyen, Maren Pein, Nicholas Pervolarakis, Jacob Insua-Rodríguez, Yanwen Gong, Grace Hernandez, Hamad Alshetaiwi, Justice Williams, Maha Rauf, Kushal Rajiv Dave, Keerti Boyapati, Aliza Hasnain, Christian Calderon, Anush Markaryan, Robert Edwards, Erin Lin, Ritesh Parajuli, Peijie Zhou, Qing Nie, Sundus Shalabi, Mark A. LaBarge, Kai Kessenbrock
Journal: Nature Genetics (2023)
A neomorphic mutation in the interferon activation domain of IRF4 causes a dominant primary immunodeficiency
Authors: Romane Thouenon, Loïc Chentout, Nidia Moreno-Corona, Lucie Poggi, Emilia Puig Lombardi, Benedicte Hoareau, Yohann Schmitt, Chantal Lagresle-Peyrou, Jacinta Bustamante, Isabelle André, Marina Cavazzana, Anne Durandy, Jean-Laurent Casanova, Lionel Galicier, Jehane Fadlallah, Alain Fischer, Sven Kracker
Journal: The Journal of Experimental Medicine (2023)

Here, we report on a heterozygous interferon regulatory factor 4 (IRF4) missense variant identified in three patients from a multigeneration family with hypogammaglobulinemia. Patients' low blood plasmablast/plasma cell and naïve CD4 and CD8 T cell counts contrasted with high terminal effector CD4 and CD8 T cell counts. Expression of the mutant IRF4 protein in control lymphoblastoid B cell lines reduced the expression of BLIMP-1 and XBP1 (key transcription factors in plasma cell differentiation). In B cell lines, the mutant IRF4 protein as wildtype was found to bind to known IRF4 binding motifs. The mutant IRF4 failed to efficiently regulate the transcriptional activity of interferon-stimulated response elements (ISREs). Rapid immunoprecipitation mass spectrometry of endogenous proteins indicated that the mutant and wildtype IRF4 proteins differed with regard to their respective sets of binding partners. Our findings highlight a novel mechanism for autosomal-dominant primary immunodeficiency through altered protein binding by mutant IRF4 at ISRE, leading to defective plasma cell differentiation.
Parkin exerts the tumor‐suppressive effect through targeting mitochondria
Authors: Xin Sun, Guiqin Ye, Yuanyuan Mai, Yuhan Shu, Lei Wang, Jianbin Zhang
Journal: Medicinal Research Reviews (2023)

Abstract The role of PARKIN in Parkinson's disease is well established but its role in cancer has recently emerged. PARKIN serves as a tumor suppressor in many cancers and loses the tumor‐suppressive function due to loss of heterozygosity and DNA copy number. But how PARKIN protects against cancer is poorly understood. Through the analysis of PARKIN substrates and their association with mitochondria, this viewpoint discussed that PARKIN exerts its anti‐cancer activity through targeting mitochondria. Mitochondria function as a convergence point for many signaling pathways and biological processes, including apoptosis, cell cycle, mitophagy, energy metabolism, oxidative stress, calcium homeostasis, inflammation, and so forth. PARKIN participates in these processes through regulating its mitochondrial targets. Conversely, these mitochondrial substrates also influence the function of PARKIN under different cellular circumstances. We believe that future studies in this area may lead to novel therapeutic targets and strategies for cancer therapy.
Heart Failure With Preserved Ejection Fraction
Authors: Margaret M. Redfield, Barry A. Borlaug
Journal: JAMA (2023)

Heart failure with preserved ejection fraction (HFpEF), defined as HF with an EF of 50% or higher at diagnosis, affects approximately 3 million people in the US and up to 32 million people worldwide. Patients with HFpEF are hospitalized approximately 1.4 times per year and have an annual mortality rate of approximately 15%.Risk factors for HFpEF include older age, hypertension, diabetes, dyslipidemia, and obesity. Approximately 65% of patients with HFpEF present with dyspnea and physical examination, chest radiographic, echocardiographic, or invasive hemodynamic evidence of HF with overt congestion (volume overload) at rest. Approximately 35% of patients with HFpEF present with "unexplained" dyspnea on exertion, meaning they do not have clear physical, radiographic, or echocardiographic signs of HF. These patients have elevated atrial pressures with exercise as measured with invasive hemodynamic stress testing or estimated with Doppler echocardiography stress testing. In unselected patients presenting with unexplained dyspnea, the H2FPEF score incorporating clinical (age, hypertension, obesity, atrial fibrillation status) and resting Doppler echocardiographic (estimated pulmonary artery systolic pressure or left atrial pressure) variables can assist with diagnosis (H2FPEF score range, 0-9; score >5 indicates more than 95% probability of HFpEF). Specific causes of the clinical syndrome of HF with normal EF other than HFpEF should be identified and treated, such as valvular, infiltrative, or pericardial disease. First-line pharmacologic therapy consists of sodium-glucose cotransporter type 2 inhibitors, such as dapagliflozin or empagliflozin, which reduced HF hospitalization or cardiovascular death by approximately 20% compared with placebo in randomized clinical trials. Compared with usual care, exercise training and diet-induced weight loss produced clinically meaningful increases in functional capacity and quality of life in randomized clinical trials. Diuretics (typically loop diuretics, such as furosemide or torsemide) should be prescribed to patients with overt congestion to improve symptoms. Education in HF self-care (eg, adherence to medications and dietary restrictions, monitoring of symptoms and vital signs) can help avoid HF decompensation.Approximately 3 million people in the US have HFpEF. First-line therapy consists of sodium-glucose cotransporter type 2 inhibitors, exercise, HF self-care, loop diuretics as needed to maintain euvolemia, and weight loss for patients with obesity and HFpEF.
Hypoxia and HIFs in Ewing sarcoma: new perspectives on a multi-facetted relationship
Authors: A. Katharina Ceranski, Martha J. Carreño-Gonzalez, Anna C. Ehlers, Maria Vittoria Colombo, Florencia Cidre-Aranaz, Thomas G. P. Grünewald
Journal: Molecular Cancer (2023)

Abstract Hypoxia develops during the growth of solid tumors and influences tumoral activity in multiple ways. Low oxygen tension is also present in the bone microenvironment where Ewing sarcoma (EwS) – a highly aggressive pediatric cancer – mainly arises. Hypoxia inducible factor 1 subunit alpha (HIF-1-a) is the principal molecular mediator of the hypoxic response in cancer whereas EWSR1::FLI1 constitutes the oncogenic driver of EwS. Interaction of the two proteins has been shown in EwS. Although a growing body of studies investigated hypoxia and HIFs in EwS, their precise role for EwS pathophysiology is not clarified to date. This review summarizes and structures recent findings demonstrating that hypoxia and HIFs play a role in EwS at multiple levels. We propose to view hypoxia and HIFs as independent protagonists in the story of EwS and give a perspective on their potential clinical relevance as prognostic markers and therapeutic targets in EwS treatment.
Enabling fully automated insulin delivery through meal detection and size estimation using Artificial Intelligence
Authors: Clara Mosquera-Lopez, Leah M. Wilson, Joseph El Youssef, Wade Hilts, Joseph Leitschuh, Deborah Branigan, Virginia Gabo, Jae H. Eom, Jessica R. Castle, Peter G. Jacobs
Journal: npj Digital Medicine (2023)

Abstract We present a robust insulin delivery system that includes automated meal detection and carbohydrate content estimation using machine learning for meal insulin dosing called robust artificial pancreas (RAP). We conducted a randomized, single-center crossover trial to compare postprandial glucose control in the four hours following unannounced meals using a hybrid model predictive control (MPC) algorithm and the RAP system. The RAP system includes a neural network model to automatically detect meals and deliver a recommended meal insulin dose. The meal detection algorithm has a sensitivity of 83.3%, false discovery rate of 16.6%, and mean detection time of 25.9 minutes. While there is no significant difference in incremental area under the curve of glucose, RAP significantly reduces time above range (glucose &gt;180 mg/dL) by 10.8% ( P = 0.04) and trends toward increasing time in range (70–180 mg/dL) by 9.1% compared with MPC. Time below range (glucose &lt;70 mg/dL) is not significantly different between RAP and MPC.
α-Synuclein conformers reveal link to clinical heterogeneity of α-synucleinopathies
Authors: Matthias Schmitz, Niccolò Candelise, Sezgi Canaslan, Hermann C. Altmeppen, Jakob Matschke, Markus Glatzel, Neelam Younas, Saima Zafar, Peter Hermann, Inga Zerr
Journal: Translational Neurodegeneration (2023)

Abstract α-Synucleinopathies, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy, are a class of neurodegenerative diseases exhibiting intracellular inclusions of misfolded α-synuclein (αSyn), referred to as Lewy bodies or oligodendroglial cytoplasmic inclusions (Papp–Lantos bodies). Even though the specific cellular distribution of aggregated αSyn differs in PD and DLB patients, both groups show a significant pathological overlap, raising the discussion of whether PD and DLB are the same or different diseases. Besides clinical investigation, we will focus in addition on methodologies, such as protein seeding assays (real-time quaking-induced conversion), to discriminate between different types of α-synucleinopathies. This approach relies on the seeding conversion properties of misfolded αSyn, supporting the hypothesis that different conformers of misfolded αSyn may occur in different types of α-synucleinopathies. Understanding the pathological processes influencing the disease progression and phenotype, provoked by different αSyn conformers, will be important for a personalized medical treatment in future.
Comparative Efficacy of Secukinumab Versus Tumor Necrosis Factor Inhibitors for the Treatment of Takayasu Arteritis
Authors: Xinping Tian, Mengtao Li, Nan Jiang, Yang Zhao, Jing Li, Yangzhong Zhou, Yahong Wang, Ying Wang, Taotao Li, Yunjiao Yang, Yanhong Wang, Peter A. Merkel, Xiaofeng Zeng
Journal: Arthritis & Rheumatology (2023)

Tumor necrosis factor (TNF) alpha and interleukin-17 (IL-17) are thought to be involved in the pathogenesis of Takayasu arteritis (TAK), and TNF inhibitors (TNFi) are recommended for the treatment of TAK. The present study was undertaken to investigate the efficacy of secukinumab, an IL-17A monoclonal antibody, compared to treatment with TNFi.This was a prospective, single-center, open-label cohort study. Patients with active TAK who did not respond to treatment with glucocorticoids combined with 2 immunosuppressive agents were treated with either secukinumab or TNFi as an add-on therapy without an increased dosage of glucocorticoids. A complete response was defined as complete resolution of signs and symptoms of active disease, normal values of inflammatory markers, no progression on imaging of involved arteries, and dose of glucocorticoid <15 mg/day. A partial response was similarly defined as a complete response except with an erythrocyte sedimentation rate <40 mm/hour and C-reactive protein level of <20 mg/liter.Nineteen patients in the secukinumab group and 34 patients in the TNFi group were enrolled. The demographic data and inflammatory markers of the 2 groups were comparable at baseline. Complete response and partial response for patients treated with secukinumab and TNFi were 31.6% and 58.8% (P = 0.057), respectively, at 3 months and 52.6% and 64.7%, respectively, at 6 months (P = 0.389).Our findings suggest that secukinumab and TNFi are effective for patients with TAK who do not respond to oral glucocorticoids and conventional immunosuppressive agents, with similar response rates at 3 and 6 months.
Extracorporeal Membrane Oxygenation and New Mental Health Diagnoses in Adult Survivors of Critical Illness—Reply
Authors: Shannon M. Fernando, Peter Tanuseputro, Kwadwo Kyeremanteng
Journal: JAMA (2023)

In Reply Our study1 demonstrated a modest association between survivorship after ECMO and new mental health diagnoses. In their Letter, Drs Li and Li hypothesize that this association may have been mediated by differences in sedation among patients exposed to ECMO.
The SARS-CoV-2 Omicron recombinant subvariants XBB, XBB.1, and XBB.1.5 are expanding rapidly with unique mutations, antibody evasion, and immune escape properties – an alarming global threat of a surge in COVID-19 cases again?
Authors: Chiranjib Chakraborty, Manojit Bhattacharya, Hitesh Chopra, Md. Aminul Islam, Gutulla Saikumar, Kuldeep Dhama
Journal: International Journal of Surgery (2023)

Chakraborty, Chiranjib PhD; Bhattacharya, Manojit; Chopra, Hitesh PhD; Islam, Md. Aminul; Saikumar, G.; Dhama, Kuldeep MVSc.PhD Author Information
We are not ‘Other’ populations: building research, education and clinical capacity around gender variance in dermatology
Authors: Gagandeep Singh, Philip Doiron, Erin Dahlke
Journal: British Journal of Dermatology (2023)

Inclusive language and health equity in dermatology are being increasingly recognized and addressed. Developing respectful language and capacity caring for transgender and gender-diverse (trans) patients are critical to building and maintaining relationships with equity-deserving communities, particularly those who have been historically pathologized and mistreated by medical institutions. The authors share several practical trans-inclusive principles to maintain respect and dignity of trans persons learned from the integration of antioppression content into their institution’s dermatology curricula and from their research, clinical and personal experiences working with trans individuals.
Political polarization of news media and influencers on Twitter in the 2016 and 2020 US presidential elections
Authors: James Flamino, Alessandro Galeazzi, Stuart Feldman, Michael W. Macy, Brendan Cross, Zhenkun Zhou, Matteo Serafino, Alexandre Bovet, Hernán A. Makse, Boleslaw K. Szymanski
Journal: Nature Human Behaviour (2023)

Social media has been transforming political communication dynamics for over a decade. Here using nearly a billion tweets, we analyse the change in Twitter's news media landscape between the 2016 and 2020 US presidential elections. Using political bias and fact-checking tools, we measure the volume of politically biased content and the number of users propagating such information. We then identify influencers-users with the greatest ability to spread news in the Twitter network. We observe that the fraction of fake and extremely biased content declined between 2016 and 2020. However, results show increasing echo chamber behaviours and latent ideological polarization across the two elections at the user and influencer levels.
Intraductal papillary neoplasms of the bile duct: a European retrospective multicenter observational study (EUR-IPNB study)
Authors: Núria Lluís, Mario Serradilla-Martín, Mar Achalandabaso, François Jehaes, Bobby V.M. Dasari, Sara Mambrilla-Herrero, Ernesto Sparrelid, Anita Balakrishnan, Frederik J.H. Hoogwater, Maria J. Amaral, Bodil Andersson, Frederik Berrevoet, Alexandre Doussot, Víctor López-López, Mohammedsuror Alsammani, Olivier Detry, Carlos Domingo-del Pozo, Nikolaos Machairas, Damján Pekli, Cándido F. Alcázar-López, Horacio Asbun, Bergthor Björnsson, Thalis Christophides, Alberto Díez-Caballero, David Francart, Colin B. Noel, Donzília Sousa-Silva, Enrique Toledo-Martínez, George N. Tzimas, Sheraz Yaqub, François Cauchy, Mikel Prieto-Calvo, Melroy A. D’Souza, Harry V.M. Spiers, Marius C. van den Heuvel, Ramón Charco, Mickaël Lesurtel, José M. Ramia
Journal: International Journal of Surgery (2023)

Background/Purpose: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare disease in Western countries. The main aim of this study was to characterize current surgical strategies and outcomes in the mainly European participating centers. Methods: A multi-institutional retrospective series of patients with a diagnosis of IPNB undergoing surgery between 1 January 2010 and 31 December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association. The textbook outcome (TO) was defined as a non-prolonged length of hospital stay plus the absence of any Clavien–Dindo grade at least III complications, readmission, or mortality within 90 postoperative days. Results: A total of 28 centers contributed 85 patients who underwent surgery for IPNB. The median age was 66 years (55–72), 49.4% were women, and 87.1% were Caucasian. Open surgery was performed in 72 patients (84.7%) and laparoscopic in 13 (15.3%). TO was achieved in 54.1% of patients, reaching 63.8% after liver resection and 32.0% after pancreas resection. Median overall survival was 5.72 years, with 5-year overall survival of 63% (95% CI: 50–82). Overall survival was better in patients with Charlson comorbidity score 4 or less versus more than 4 ( P =0.016), intrahepatic versus extrahepatic tumor ( P =0.027), single versus multiple tumors ( P =0.007), those who underwent hepatic versus pancreatic resection ( P =0.017), or achieved versus failed TO ( P =0.029). Multivariable Cox regression analysis showed that not achieving TO (HR: 4.20; 95% CI: 1.11–15.94; P =0.03) was an independent prognostic factor of poor overall survival. Conclusions: Patients undergoing liver resection for IPNB were more likely to achieve a TO outcome than those requiring a pancreatic resection. Comorbidity, tumor location, and tumor multiplicity influenced overall survival. TO was an independent prognostic factor of overall survival.
Pharmacogenomic profiling reveals molecular features of chemotherapy resistance in IDH wild-type primary glioblastoma
Authors: Yoonhee Nam, Harim Koo, Yingxi Yang, Sang Shin, Zhihan Zhu, Donggeon Kim, Hee Jin Cho, Quanhua Mu, Seung Won Choi, Jason K. Sa, Yun Jee Seo, Yejin Kim, Kyoungmin Lee, Jeong-Woo Oh, Yong-Jun Kwon, Woong-Yang Park, Doo-Sik Kong, Ho Jun Seol, Jung-Il Lee, Chul-Kee Park, Hye Won Lee, Yeup Yoon, Jiguang Wang
Journal: Genome Medicine (2023)

Abstract Background Although temozolomide (TMZ) has been used as a standard adjuvant chemotherapeutic agent for primary glioblastoma (GBM), treating isocitrate dehydrogenase wild-type (IDH-wt) cases remains challenging due to intrinsic and acquired drug resistance. Therefore, elucidation of the molecular mechanisms of TMZ resistance is critical for its precision application. Methods We stratified 69 primary IDH-wt GBM patients into TMZ-resistant ( n = 29) and sensitive ( n = 40) groups, using TMZ screening of the corresponding patient-derived glioma stem-like cells (GSCs). Genomic and transcriptomic features were then examined to identify TMZ-associated molecular alterations. Subsequently, we developed a machine learning (ML) model to predict TMZ response from combined signatures. Moreover, TMZ response in multisector samples (52 tumor sectors from 18 cases) was evaluated to validate findings and investigate the impact of intra-tumoral heterogeneity on TMZ efficacy. Results In vitro TMZ sensitivity of patient-derived GSCs classified patients into groups with different survival outcomes ( P = 1.12e−4 for progression-free survival (PFS) and 3.63e−4 for overall survival (OS)). Moreover, we found that elevated gene expression of EGR4 , PAPPA , LRRC3 , and ANXA3 was associated to intrinsic TMZ resistance. In addition, other features such as 5-aminolevulinic acid negative, mesenchymal/proneural expression subtypes, and hypermutation phenomena were prone to promote TMZ resistance. In contrast, concurrent copy-number-alteration in PTEN , EGFR , and CDKN2A/B was more frequent in TMZ-sensitive samples (Fisher’s exact P = 0.0102), subsequently consolidated by multi-sector sequencing analyses. Integrating all features, we trained a ML tool to segregate TMZ-resistant and sensitive groups. Notably, our method segregated IDH-wt GBM patients from The Cancer Genome Atlas (TCGA) into two groups with divergent survival outcomes ( P = 4.58e−4 for PFS and 3.66e−4 for OS). Furthermore, we showed a highly heterogeneous TMZ-response pattern within each GBM patient using in vitro TMZ screening and genomic characterization of multisector GSCs. Lastly, the prediction model that evaluates the TMZ efficacy for primary IDH-wt GBMs was developed into a webserver for public usage ( http://www.wang-lab-hkust.com:3838/TMZEP ). Conclusions We identified molecular characteristics associated to TMZ sensitivity, and illustrate the potential clinical value of a ML model trained from pharmacogenomic profiling of patient-derived GSC against IDH-wt GBMs.
Spinal Cord Burst Stimulation vs Placebo Stimulation for Patients With Chronic Radicular Pain After Lumbar Spine Surgery
Authors: Simon Thomson, Jan Willem Kallewaard, Kliment Gatzinsky
Journal: JAMA (2023)

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